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Biomedical subjects

Naoto Ashizawa

Publications and source records attributed to Naoto Ashizawa.

12 recordsLinked to original sources
PubMed2007

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.

Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulin-sensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulin-sensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-beta, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-beta1/GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.

Angiotensin II↗
PubMed2006

Risk of development of abdominal aortic aneurysm and dissection of thoracic aorta in a postpartum woman with Marfan's syndrome.

A 24-year-old pregnant woman with Marfan's syndrome delivered by cesarean section during the 38th week of gestation. Although aortic root dilatation did not increase during pregnancy, three months after delivery, the patient noticed a pulsatile abdominal mass. Aortic aneurysm was diagnosed and surgical replacement of the infrarenal abdominal aorta to the common iliac arteries and reconstruction of the inferior mesenteric artery were performed. Moreover, the patient subsequently developed a Stanford type B thoracic aortic dissection, even after more than four months of beta-blockade.

Adrenergic beta-Antagonists↗
PubMed2006

[Plasma B-type natriuretic peptide (BNP) measuring].

Brain or B-type natriuretic peptide (BNP) is a potent natriuretic, diuretic and vasorelaxant peptide and inhibits sympathetic tone, the renin-angiotensin-aldosterone system, and synthesis of vasoconstrictive molecules. The major source of plasma BNP is the cardiac ventricles. Elevated plasma BNP concentrations correlate with increased left ventricular (LV) filling pressure. Therefore BNP is a useful biomarkers as a screening tool for LV dysfunction. It also is a strong diagnostic indicator for both systolic and diastolic LV dysfunction. Measurement of plasma BNP is proved to be not only an efficient but also a cost effective screening tool for identifying patients with acute dyspnea of unknown etiology.

Biomarkers↗
PubMed2005

Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy.

Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical phenotypes of "idiopathic" cardiomyopathy. Recent molecular genetic analyses have now revealed that "idiopathic" cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.

Aged↗
PubMed2004

GH suppresses TGF-beta-mediated fibrosis and retains cardiac diastolic function.

The aims of this study were to elucidate the molecular mechanism by which growth hormone (GH) excess is anti-fibrotic in vitro and in vivo model. The in vivo model GH excess showed a significant increase of relative wall thickness with no concomitant disturbance of cardiac diastolic function. Western blot for extracellular matrix (ECM) structural proteins showed minimal change in the GH treatment group, compared to an Angiotensin II (Ang II) subpressor dose group. In cultured cardiac fibroblasts, we investigated the abundance of ECM proteins, phosphorylation of p38 mitogen-activated protein kinase (MAPK), and transforming growth factor-beta (TGF-beta)-specific transcriptional activity. GH down-regulated the expression of PAI-1 and fibronectin proteins activated by TGF-beta. In reporter assays, GH, but not insulin-like growth factor-1 (IGF-1), reduced TGF-beta-specific transcriptional activity. Moreover, GH markedly down-regulated TGF-beta-induced phosphorylation of p38 MAPK. These results demonstrated that a chronic excess of GH have an anti-fibrotic effect on cardiac remodeling, probably through a down-regulation of TGF-beta signaling via de-phosphorylation of p38 MAPK.

Angiotensin II↗
PubMed2004

Sotalol-induced coronary spasm in a patient with dilated cardiomyopathy associated with sustained ventricular tachycardia.

A 54-year-old man with severe left ventricular dysfunction due to dilated cardiomyopathy was referred to our hospital for symptomatic incessant sustained ventricular tachycardia (VT). After the administration of nifekalant hydrochloride, sustained VT was terminated. An alternate class III agent, sotalol, was also effective for the prevention of VT. However, one month after switching over nifekalant to sotalol, a short duration of ST elevation was documented in ECG monitoring at almost the same time for three consecutive days. ST elevation with chest discomfort disappeared since he began taking long-acting diltiazem. Coronary vasospasm may be induced by the non-selective beta-blocking properties of sotalol.

Anti-Arrhythmia Agents↗
PubMed2003

A rare case of aortic tube graft occlusion 35 years after coarctectomy.

A 52-year-old male with a history of repair of aortic coarctation by prosthetic tube graft replacement 35-years ago developed anterior spinal artery syndrome caused by acute functional occlusion of the aorta at the repair site where pseudoaneurysm formation was observed. The patient was rescued by an emergency axillofemoral bypass, and residual hypertension in upper limbs was improved by elective ascending aorta-descending aorta bypass grafting.

Aneurysm, False↗
PubMed2003

Administration of nifedipine CR immediately after awakening prevents a morning surge in hypertensive patients. Case report of three cases.

Although the blood pressure-lowering action of some long-acting calcium antagonists may last more than 24 h, some patients taking this drug still experience a morning surge, i.e. an early morning increase in blood pressure. We evaluated this morning surge in three hypertensive patients with morning surge after administration of antihypertensive drugs including nifedipine CR. Nifedipine CR is one of the once-a-day formulations of nifedipine, which after administration, results in two peaks in the plasma concentration of nifedipine. The first concentration peak of occurs 3 h after administration and the second around 12 h after intake. When the time of intake of nifedipine CR was changed from after breakfast to immediately after awakening, the morning surge was suppressed in these patients without the use of other drugs such as alpha- or beta-blockers. Administration of nifedipine CR immediately after awakening is one option that can be used to prevent morning surge as well as to control blood pressure throughout the day.

Adult↗
PubMed2003

Hypercalcemia due to vitamin D intoxication with clinical features mimicking acute myocardial infarction.

We report a case of hypercalcemia in an elderly patient due to vitamin D intoxication with clinical features and electrocardiogram (ECG) findings mimicking acute myocardial infarction. A 78-year-old man was referred to our department with symptoms of general fatigue, anorexia and chest pain. The ECG demonstrated ST elevation in leads V1 to V3 and diffuse T wave flattening, resulting in myocardial infarction being suspected. However, his symptoms, including chest pain, gradually improved and the ECG returned to normal in accordance with a fall in his serum calcium level. We introduce the use of QaTc interval shortening in differentiating ST-T changes of hypercalcemia from those of true myocardial ischemia.

Aged↗
PubMed2003

Segmental mediolytic arteriopathy involving celiac to splenic and left renal arteries.

A 46-year-old man presented with a huge splenic artery dissecting aneurysm that had been incidentally found and was successfully resected before rupture. The histopathologic findings were compatible with segmental mediolytic arteriopathy (SMA). Simultaneous involvement of the left renal and right common iliac artery was observed. The patient was also found to have an adrenocortical adenoma, gastrointestinal stromal tumor, hepatocellular carcinoma and schizophrenia. The relationship between SMA and other accompanying diseases was discussed.

Adrenal Cortex Neoplasms↗
PubMed2002

Norepinephrine enhances fibrosis mediated by TGF-beta in cardiac fibroblasts.

Cardiac fibrosis results from proliferation of interstitial fibroblasts and concomitant increased biosynthesis of extracellular matrix (ECM) components and is often complicated by cardiac hypertrophy. This study was conducted to investigate whether norepinephrine (NE) potentiates transforming growth factor-beta (TGF-beta)-induced cardiac fibrosis. The expression of the cardiac ECM proteins, plasminogen activator inhibitor-1 (PAI-1), fibronectin, and collagen type I, was examined by Western blotting using extracts from neonatal rat primary cardiac fibroblasts. In cardiac fibroblasts, treatment with a combination of NE and TGF-beta1 increased cell proliferation and ECM expression. Luciferase assays were conducted to clarify the effect of NE on TGF-beta signaling. TGF-beta1 (1 ng/mL) increased the specific signaling activity 2-fold, whereas the combination of NE (10 micro mol/L) and TGF-beta1 (1 ng/mL) resulted in an approximate 10-fold increase in specific signaling activity. We confirmed that treatment with NE markedly enhances TGF-beta-induced phosphorylation of activating transcription factor 2 (ATF-2). These results indicated that NE has a synergistic effect on TGF-beta signaling. To determine whether this activation by NE was mediated by the TGF-beta1 receptor, we used a dominant negative vector of the TGF-beta1 type II receptor, and the synergistic effects were inhibited. Furthermore, this synergistic effect was attenuated by a specific inhibitor of p38, SB203680. These data indicate that NE enhances cardiac fibrosis through TGF-beta1 post-receptor signaling, predominantly via the p38 MAP kinase pathway.

Activating Transcription Factor 2↗